An implantable tissue monitoring system is proposed to address the limitations of existing instrumentation for tissue perfusion monitoring for a variety of clinical applications. The implanted system is intended as a minimally-invasive screening tool that provides real-time tissue perfusion and oxygen assessment to prompt physician attention and the application of established diagnostics and invasive corrective procedures, in particular for liver transplant. The system relies on photonics-based measurements coupled with integrated signal processing and data telemetry to provide real-time monitoring of tissue perfusion. The methodology and implementation are directed towards surgical and post-surgical procedures and have application to a number of additional monitoring scenarios including emergency medicine and critical care. Miniaturization will be accomplished using microfabrication techniques allowing complete implantation of the sensor system in the precise region of interest, either as a subdermal or deep tissue implant. Signal processing will be incorporated in the implanted micro-system to reduce the data communication requirements and potentially allow automated process control. A three-wavelength system will initially be designed and tested in a number of clinical scenarios to assess relative levels of perfusion and to establish clinical protocols for use of this technique. Additional capabilities for quantification of arterial and venous oxygen saturation will be developed to permit assessment of organ oxygen utilization. Biocompatible encapsulation materials will be utilized allowing long-term monitoring scenarios. The use of spread-spectrum RF data communications will both assure high-integrity data telemetry and avoid RF interference to existing medical instrumentation systems. This will also permit deployment of multiple sensors in close proximity for more comprehensive patient monitoring applications. The end goal of the project is to produce a working implantable system with well-established clinical applications and associated protocols demonstrated through animal testing. A strong collaboration of established medical, bioengineering, and engineering professionals with a published history of collaboration exists among the Principal Investigator, Mark A. Wilson, MD, PhD (University of Pittsburgh), and Lead Investigators, M. Nance Ericson, PhD (Oak Ridge National Laboratory) and Gerard L. Cote, PhD (Texas A&M University). Dr. Wilson is responsible for overall study coordination and clinical application studies. Dr. Ericson leads efforts for development of electronics, and Dr. Cote is responsible for optical sensing strategies. This collaboration provides the expertise and research facilities necessary to successfully address important clinical patient monitoring problems using a combination of medical photonics and smart medical instrumentation in a unique integrated package.